Merck’s new formulation of the mega-blockbuster Keytruda, made in collaboration with Alteogen, could help to keep the drug’s patent cliff at bay.
In a push to keep the Keytruda gravy train on the tracks, Merck has shown that a subcutaneous formulation of the cancer drug equaled—and in some cases bested—the original intravenous formulation.
The injectable formulation would allow much faster administration of the drug, providing patients with faster treatment at a medical center and easing administration. But it is also the latest attempt in Merck’s quest to extend the patent on Keytruda. The current patent for the drug—which brought in $29 billion last year—is set to expire in 2028.
The pivotal phase III study in patients with metastatic non-small cell lung cancer, dubbed 3475A-D77, met the primary endpoint of non-inferiority to the IV version. In two trial markers, the subcutaneous formulation actually beat the IV version, achieving a higher blood concentration after administration.
The subcutaneous version achieved a slightly higher overall response rate when combined with chemotherapy (45.4% versus 42.1% for IV), and a slightly higher progression-free survival (8.1 months versus 7.8 for IV).
Merck noted that median overall survival has not yet been met in either trial, meaning that more than half of the patients in the trial were still alive as of the data cut-off.
Patients also spent about half the time in the clinic receiving the treatment as compared to the IV version, according to the readout.
Adverse effects occurred at about the same rate—47%—for both formulations, with a death rate related to the treatment of 3.6% for the subcutaneous drug and 2.4% for the IV version.
Based on these results, featured Thursday at the European Lung Cancer Congress (ELCC) 2025 and simultaneously published in Annals of Oncology, the FDA has accepted a biologics license application (BLA) for the new formulation across all of Keytruda’s previously approved solid tumor indications. The agency set a decision date of September 23, 2025.
Previous data from MK-3475A-D77 in November 2024 showed that the subcutaneous version was equally effective in treating metastatic non-small cell lung cancer compared to the IV infusion. At the time, Guggenheim analysts said those results were “an important step for the longevity of the Keytruda franchise.”
Thursday, Merck added equivalent pharmacokinetics to the record to build its case for approval. The New Jersey-based pharma compared the original IV version of the drug with Keytruda plus berahyaluronidase alfa, a human protein manufactured in a collaboration with Alteogen that allows drugs to be administered in a subcutaneous injection. Patients in the trial were newly diagnosed with metastatic non-small cell lung cancer.
Merck is simultaneously conducting a Phase II patient preference study called 3475A-F11, evaluating whether patients show a preference between the IV or subcutaneous version of Keytruda, according to Merck’s announcement.
